A retrospective descriptive investigation into the clinical profile of HIV patients in the North West Province switched to third-line regimens

Abstract

South Africa has the largest human immunodeficiency virus (HIV) epidemic in the world, with the number of people living with HIV increasing to 7.06 million by mid-2017. In October 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) implemented the 90-90-90 targets. This means 90% of people living with HIV should know their HIV status, 90% of people diagnosed with HIV should receive antiretroviral therapy (ART) and 90% of those receiving ART should be virally suppressed by the end of 2020 to end the epidemic as a public threat by 2030. The number of patients experiencing virological failure will inevitably increase due to greater access and prolonged exposure to antiretroviral therapy (ART); this may increase the need for third-line antiretroviral therapy (TLART) in a resource-limited setting such as South Africa. The main overarching aim of this all-inclusive retrospective descriptive investigation was to create a typical clinical profile of adult patients initiated onto TLART in the North West Province of South Africa by reporting and describing the demographics, certain clinical variables and viral resistance patterns recorded from patient health records. Approval to conduct this study was obtained from the North West Department of Health, Policy, Planning, Research, Monitoring and Evaluation Directorate, Mahikeng, on 13 January 2017. Ethics approval was obtained from the North-West University, Health Research Ethics Committee, with approval number NWU-00340-16-A1, on 13 March 2017 with a protocol amendment to replace and add an additional study-site, approved on 25 May 2017. All recorded data were analysed by means of descriptive statistics, with median (interquartile range, IQR: 25th to 75th) used for variables without a normal distribution and percentages (frequencies) used for categorical variables. The Stanford University HIV Drug Resistance Database was used to interpret the clinical significance of drug resistant mutations identified in the study population. Twenty-one adult patients were included in this cohort, 17 were females and four males, located in three districts and four hospitals of the North West Province. The median age at HIV diagnosis was 34 years (IQR: 30.25-36.75) and 46 years (IQR: 40-48.50), respectively, at TLART initiation. At baseline, a median CD4 count and viral load (VL) of 68.50 cells/μL (IQR: 40.75-127.75) and 98 000 copies/ml (IQR: 45 569-820 000), were reported respectively. At failure of first-line ART, the CD4 count and VL were 79.00 cells/ μL (IQR: 26.5-124) and 100 000 copies/ml (IQR: 42 085-248 852), and at the end of second-line ART failure the CD4 count and VL were 119 cells/μL (IQR: 61.25-201.25) and 73 196 copies/ml (IQR: 26 210-197 007), respectively. Clinical monitoring markers documented included, serum creatinine, haemoglobin, mean corpuscular volume (MCV), alanine transferase (ALT) and total cholesterol at baseline and at first- and second-line ART failure. Some of these results, however, were incomplete due to missing data in patient health records, thus drawing any valuable conclusion to contribute to the description of a typical clinical profile was not possible. The median duration from HIV diagnosis to first-line ART initiation was 101 days (IQR: 36.50-366.75), on first-line ART it was 1 269 days (IQR: 765-2 343), on second-line ART 1 512 days (IQR: 706-2 096) and between second-line ART failure and TLART initiation, 71 days (IQR: 57.5-126). The first-line ART regimen, most often initiated was (n=11) lamivudine (3TC), stavudine (d4T) and efavirenz (EFV) which occurred prior to 2010 and the PI-based second-line ART regimen was (n=7) lamivudine (3TC), zidovudine (AZT) and ritonavir boosted lopinavir (LPV/r). The resistance mutations most prevalent for protease inhibitors (PIs) (n=20) were M46I (75%), V82A (65%) and I54V (65%). The median number of total PI resistance mutations (major and minor) found per patient was three mutations (IQR: 2-3). The resistance mutations most prevalent for nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) (n=18) were M184V (89.47%), D67N (31.58%), M41L (26.31%) and T215Y, and V118I (21.05%) and for non-nucleoside reverse transcriptase inhibitors (NNRTIs) (n=17): K103N (47.01%) and G190A (23.52%). High-level of resistance most prevalent in this cohort for PIs were against nelfinavir/r (85.7%), indinavir/r (81.0%), lopinavir/r (76.2%), fosamprenavir/r (66.7%) and atazanavir/r (57.1%); NRTIs were emtricitabine (95.2%), lamivudine (95.2%) and zidovudine (52.4%); NNRTIs were nevirapine (76.2%) and efavirenz (71.4%). A constant low CD4 count and detectable VL >50 copies/mL throughout the duration of ART were found in this study population. The duration between second-line ART failure and TLART initiation found in this study may contribute to an increased number of PI resistance mutations, after a median duration of 71 days (IQR: 58-126). High-level cross-resistance between PIs and a combination of major and minor PI resistant mutations were found in most patients in this study population, but even with limited data numbers, certain markers were identified and used to create an initial clinical profile of the patients. Results from this study can form the basis for larger studies in South Africa, to create more successful TLART management and care programmes. One of the limitations of this retrospective descriptive investigation was the missing data at certain time-points, as the majority of the retrospective data dated back to 2004 and the National ART guidelines changing several times with regards to the regimen compositions, efficacy and toxicity tests and frequencies of monitoring intervals. This study highlighted important demographic and clinical characteristics that may improve the management and care of HIV patients and possibly prevent patients from failing their respective ART regimens. It also highlighted the importance of individualised HIV management and care programs in each healthcare facility, intensified adherence counselling and earlier drug resistance testing for improved and more effective and optimised ART in the future.